Abstract
Object. The PC12 cells are well known for their ability to secrete dopamine and levodopa. In multiple animal models encapsulated PC12 cells have been shown to ameliorate parkinsonian symptoms when transplanted into the striatum; this technique is expected to be effective clinically as well. The present study was performed using nonhuman primates to ensure that the transplantation of encapsulated PC12 cells is likely to be both safe and effective in human clinical trials. Methods. Unencapsulated or encapsulated PC12 cells were implanted into the brains of Japanese monkeys (Macaca fuscata). Histological and immunocytochemical analyses were performed 1, 2, 4, and 8 weeks posttransplantation on the unencapsulated cells and 2, 4, and 8 weeks after transplantation on the encapsulated cells. The survival of the PC12 cells inside the capsule was determined by measuring the amounts of dopamine and levodopa released from the capsules after removal from the striatum. Magnetic resonance imaging was performed in both unencapsulated and encapsulated PC12 cell-grafted groups. Due to the immunological reaction of the host brain no unencapsulated PC12 cells remained in the grafted area 8 weeks after transplantation. On the contrary, encapsulated PC12 cells retrieved from the host brain continued to release dopamine and levodopa even 8 weeks after implantation. The host's reaction to the PC12-loaded capsule was much weaker than that to the unencapsulated PC12 cells. Conclusions. These results suggest that the transplantation of encapsulated PC12 cells could be a safe and effective treatment modality for Parkinson disease in human patients.
| Original language | English |
|---|---|
| Pages (from-to) | 874-881 |
| Number of pages | 8 |
| Journal | Journal of Neurosurgery |
| Volume | 98 |
| Issue number | 4 |
| Publication status | Published - Apr 1 2003 |
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Keywords
- Macaca fuscata
- Neural transplantation
- Nonhuman primate
- Parkinson disease
- PC12 cell
ASJC Scopus subject areas
- Clinical Neurology
- Neuroscience(all)
Cite this
Stereotactic transplantation of a dopamine-producing capsule into the striatum for treatment of Parkinson disease : A preclinical primate study. / Yoshida, Hideyuki; Date, Isao; Shingo, Tetsuro; Fujiwara, Kenjiro; Kobayashi, Kazuki; Miyoshi, Yasuyuki; Ohmoto, Takashi.
In: Journal of Neurosurgery, Vol. 98, No. 4, 01.04.2003, p. 874-881.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Stereotactic transplantation of a dopamine-producing capsule into the striatum for treatment of Parkinson disease
T2 - A preclinical primate study
AU - Yoshida, Hideyuki
AU - Date, Isao
AU - Shingo, Tetsuro
AU - Fujiwara, Kenjiro
AU - Kobayashi, Kazuki
AU - Miyoshi, Yasuyuki
AU - Ohmoto, Takashi
PY - 2003/4/1
Y1 - 2003/4/1
N2 - Object. The PC12 cells are well known for their ability to secrete dopamine and levodopa. In multiple animal models encapsulated PC12 cells have been shown to ameliorate parkinsonian symptoms when transplanted into the striatum; this technique is expected to be effective clinically as well. The present study was performed using nonhuman primates to ensure that the transplantation of encapsulated PC12 cells is likely to be both safe and effective in human clinical trials. Methods. Unencapsulated or encapsulated PC12 cells were implanted into the brains of Japanese monkeys (Macaca fuscata). Histological and immunocytochemical analyses were performed 1, 2, 4, and 8 weeks posttransplantation on the unencapsulated cells and 2, 4, and 8 weeks after transplantation on the encapsulated cells. The survival of the PC12 cells inside the capsule was determined by measuring the amounts of dopamine and levodopa released from the capsules after removal from the striatum. Magnetic resonance imaging was performed in both unencapsulated and encapsulated PC12 cell-grafted groups. Due to the immunological reaction of the host brain no unencapsulated PC12 cells remained in the grafted area 8 weeks after transplantation. On the contrary, encapsulated PC12 cells retrieved from the host brain continued to release dopamine and levodopa even 8 weeks after implantation. The host's reaction to the PC12-loaded capsule was much weaker than that to the unencapsulated PC12 cells. Conclusions. These results suggest that the transplantation of encapsulated PC12 cells could be a safe and effective treatment modality for Parkinson disease in human patients.
AB - Object. The PC12 cells are well known for their ability to secrete dopamine and levodopa. In multiple animal models encapsulated PC12 cells have been shown to ameliorate parkinsonian symptoms when transplanted into the striatum; this technique is expected to be effective clinically as well. The present study was performed using nonhuman primates to ensure that the transplantation of encapsulated PC12 cells is likely to be both safe and effective in human clinical trials. Methods. Unencapsulated or encapsulated PC12 cells were implanted into the brains of Japanese monkeys (Macaca fuscata). Histological and immunocytochemical analyses were performed 1, 2, 4, and 8 weeks posttransplantation on the unencapsulated cells and 2, 4, and 8 weeks after transplantation on the encapsulated cells. The survival of the PC12 cells inside the capsule was determined by measuring the amounts of dopamine and levodopa released from the capsules after removal from the striatum. Magnetic resonance imaging was performed in both unencapsulated and encapsulated PC12 cell-grafted groups. Due to the immunological reaction of the host brain no unencapsulated PC12 cells remained in the grafted area 8 weeks after transplantation. On the contrary, encapsulated PC12 cells retrieved from the host brain continued to release dopamine and levodopa even 8 weeks after implantation. The host's reaction to the PC12-loaded capsule was much weaker than that to the unencapsulated PC12 cells. Conclusions. These results suggest that the transplantation of encapsulated PC12 cells could be a safe and effective treatment modality for Parkinson disease in human patients.
KW - Macaca fuscata
KW - Neural transplantation
KW - Nonhuman primate
KW - Parkinson disease
KW - PC12 cell
UR - http://www.scopus.com/inward/record.url?scp=0037385053&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037385053&partnerID=8YFLogxK
M3 - Article
C2 - 12691415
AN - SCOPUS:0037385053
VL - 98
SP - 874
EP - 881
JO - Journal of Neurosurgery
JF - Journal of Neurosurgery
SN - 0022-3085
IS - 4
ER -